# US 12,643,955 B2 · Humanized anti-GPC-1 antibody

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- Number: US 12,643,955 B2
- Document ID: US12643955B2
- Status: Granted
- Kind: B2
- Application number: 18/009,024
- Filed: 2021-06-10
- Published: 2023-08-10
- Granted: 2026-06-02
- Earliest claimed: 2020-06-11
- Assignees: Iwate Medical University
- Applicants: Iwate Medical University
- Inventors: Tetsuji Naka; Satoshi Serada
- Web page: https://patentgrep.com/patent/US12643955B2

## CPC

- C07K 16/303: {Liver or Pancreas}
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6859: {the tumour determinant being from liver or pancreas cancer cell}
- A61K 47/6877: {the antibody being an immunoglobulin containing regions, domains or residues from different species}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure provides a humanized antibody that specifically binds to Glypican-1 (GPC-1), and also provides technologies, methods, medicines, and the like related to the humanized antibody. In one aspect, the present disclosure provides a humanized anti-GPC-1 monoclonal antibody that has a high affinity for GPC-1 and has high internalization activity in GPC-1-positive cells. In another aspect, the present disclosure also provides a composition for preventing or treating Glypican-1-positive cancer that includes a complex of a humanized anti-GPC-1 monoclonal antibody and a medicine having cytotoxic activity.

## Claims

### Claim 1

A humanized anti-GPC-1 antibody or an antigen-binding fragment thereof, comprising:
heavy-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 28 to 30, respectively, and
(a) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 31 to 33, respectively, or
(b) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 37 to 39, respectively, or
(c) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 40 to 42, respectively, or
(d) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 43 to 45, respectively, or
(e) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 49 to 51, respectively, or
(f) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 55 to 57, respectively, or
(g) light-chain CDRs 1 to 3 having amino acid sequences set forth in SEQ ID NOs: 58 to 60, respectively.

### Claim 2 (depends on 1)

The humanized antibody or the antigen-binding fragment thereof according to claim 1, comprising:
a heavy-chain variable region having an amino acid sequence with at least 90% identity to an amino acid sequence set forth in SEQ ID NO: 7; and/or
a light-chain variable region having an amino acid sequence with at least 90% identity to an amino acid sequence selected from the group consisting of amino acid sequences set forth in SEQ ID NOs: 8, 10, 11, 12, 14, 16 and 17; or
a light-chain variable region having an amino acid sequence selected from the group consisting of amino acid sequences set forth in SEQ ID NOs: 8, 10, 11, 12, 14, 16 and 17.

### Claim 3 (depends on 1)

The humanized antibody or the antigen-binding fragment thereof according to claim 1, wherein an epitope of the antibody includes positions 339 to 358 and/or 388 to 421 of SEQ ID NO: 2.

### Claim 4 (depends on 1)

The humanized antibody or the antigen-binding fragment thereof according to claim 1, wherein
the antibody binds to GPC-1 with a KD of 1.02E−8 or less, the KD being based on analysis using a surface plasmon resonance technique.

### Claim 5 (depends on 1)

A complex of the humanized antibody or the antigen-binding fragment thereof according to claim 1, and a medicine having cytotoxic activity.

### Claim 6 (depends on 5)

The complex according to claim 5, wherein
the humanized antibody or the antigen-binding fragment thereof is operably linked to the medicine having cytotoxic activity via a linker.

### Claim 7 (depends on 5)

The complex according to claim 5, wherein
the medicine having cytotoxic activity is selected from the group consisting of monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), DM1, DM4, calicheamicin, duocarmycin, pyrrolobenzodiazepine (PBD), and topoisomerase inhibitors.

### Claim 8 (depends on 6)

The complex according to claim 6,
wherein the medicine having cytotoxic activity has cell membrane permeability.

### Claim 9 (depends on 6)

The complex according to claim 6, wherein
the medicine having cytotoxic activity is selected from MMAE, PBD, Eribulin, SN-38, Dxd, and DM4.

### Claim 10 (depends on 6)

The complex according to claim 6, wherein
the linker is selected from the group consisting of an enzyme cleavable linker, an acid labile linker, and a disulfide linker.

### Claim 11 (depends on 6)

The complex according to claim 6, wherein
the linker is a cleavable linker capable of being cleaved by cathepsin B.

### Claim 12 (depends on 5)

The complex according to claim 5, wherein
the complex has an IC50 of about 0.1 nM or less in a GPC-1-positive cell.

### Claim 13 (depends on 12)

A method for preventing or treating GPC-1-positive cancer in a subject, the method comprising:
administering the complex according to claim 12 to the subject.

### Claim 14 (depends on 13)

The method according to claim 13, wherein
the GPC-1-positive cancer is selected from esophageal cancer, pancreatic cancer, bile duct cancer, cervical cancer, lung cancer, head and neck cancer, breast cancer, uterine leiomyosarcoma, prostate cancer, oral squamous cell cancer, and any combinations thereof.

### Claim 15 (depends on 13)

The method according to claim 13, wherein
wherein the GPC-1-positive cancer is esophageal cancer or pancreatic cancer.

### Claim 16 (depends on 13)

The method according to claim 13, wherein
the GPC-1-positive cancer has cancer-associated fibroblasts (CAFs).

### Claim 17 (depends on 13)

The method according to claim 13, the method, further comprising:
administering an immune checkpoint inhibitor.

### Claim 18 (depends on 17)

The method according to claim 17, wherein
the immune checkpoint inhibitor is an anti-PD-1 antibody.